BIOORGANIC CHEMISTRY
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2022
·
IF 5.307
Na Jiang,Liqiu Quan,Yan Zhou,Yungyi Cheng,Hongmei Li,Xuanqin Chen,Rongtao Li,Dan Liu
Triptolide (TP) is a major active compound derived from the traditional Chinese medicine Tripterygium wilfordii . TP has been reported to inhibit the infection of HIV and a few other viruses. However, the antiviral spectrum and the underlying mechanisms of TP are incompletely defined. TP derivatives were designed, synthesized, and evaluated for anti-influenza activity against the influenza A virus in this study. All of them exhibited activities against oseltamivir sensitive influenza A/WSN/33 virus (H1N1) and oseltamivir resistant influenza A/PR/8/33 virus (H1N1) with low cytotoxicity in vitro . In our present study, TP derivatives probably suppressed influenza virus replication through inhibiting ribonucleoprotein complex nucleus export of influenza A virus by binding with viral nucleoprotein. Moreover, TP derivatives downregulated influenza A virus-induced macrophage cytokine storm in a dose-dependent manner, through inhibiting nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome signaling. Taken together, TP derivatives suppressed influenza A virus replication by directly targeting NP and regulating innate immune responses induced by influenza A virus infection, which suggested that TP derivatives might be prospective candidates for potent antivirals.
研究领域:
药理学
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病毒学
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免疫学
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PubMed
高影响因子
TOXICOLOGY LETTERS
·
2018
·
IF 3.166
Yisen Cheng,Gaojian Chen,Li Wang,Jiamin Kong,Ji Pan,Yue Xi,Feihai Shen,Zhiying Huang
Triptolide is a major active ingredient of tripterygium glycosides, used for the therapy of immune and inflammatory diseases. However, its clinical applications are limited by severe male fertility toxicity associated with decreased sperm count, mobility and testicular injures. In this study, we determined that triptoide-induced mitochondrial dysfunction triggered reduction of lactate and dysregulation of fatty acid metabolism in mouse Sertoli cells. First, triptolide induced mitochondrial damage through the suppressing of proliferator-activated receptor coactivator-1 alpha (PGC-1α) activity and protein. Second, mitochondrial damage decreased lactate production and dysregulated fatty acid metabolism. Finally, mitochondrial dysfunction was initiated by the inhibition of sirtuin 1 (SIRT1) with the regulation of AMP-activated protein kinase (AMPK) in Sertoli cells after triptolide treatment. Meanwhile, triptolide induced mitochondrial fatty acid oxidation dysregulation by increasing AMPK phosphorylation. Taken together, we provide evidence that the mechanism of triptolide-induced testicular toxicity under mitochondrial injury may involve a metabolic change.
研究领域:
药理学
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毒理学
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生殖生物学
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细胞代谢
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PubMed
高影响因子
HUMAN & EXPERIMENTAL TOXICOLOGY
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2021
·
IF 2.903
Hai-Yan Jiang,Yan-Ni Bao,Feng-Mei Lin,Yong Jin
Triptolide (TP), the main active compound extracted from medicine- tripterygium wilfordii Hook f. (TWHF). It has anti-tumor and immunomodulatory properties. Our study aimed to investigate the mechanisms of hepatotoxicity treated with TP in vivo and in vitro, as well as their relationship with the NF-κB (p65) signal pathway; and to assess TP-induced hepatotoxicity after CYP2E1 modulation by the known inhibitor, clomethiazole, and the known inducer, pyrazole. Mice were given TP to cause liver injury and IHHA-1 cells were given TP to cause hepatocyte injury. The enzyme activity and hepatotoxicity changed dramatically when the CYP2E1 inhibitor and inducer were added. In comparison to the control group, the enzyme inducer increased the activity of CYP2E1, whereas the enzyme inhibitor had the opposite effect. Our findings suggest that TP is an inducer of CYP2E1 via a time-dependent activation mechanism. In addition, TP can promote oxidative stress, inflammatory and involving the NF-κB (p65) signal pathway. Therefore, we used triptolide to stimulate C57 mice and IHHA-1 cells to determine whether TP can promote oxidative stress and inflammation by activating CYP2E1 in response to exacerbated liver damage and participate in NF-κB (p65) signaling pathway.
研究领域:
药理学
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毒理学
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分子生物学
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PubMed
高影响因子
JOURNAL OF INSECT PHYSIOLOGY
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2022
·
IF 2.608
Junjun Zhang,Zhengwei Wang,Katrina Klett,Yufeng Qu,Ken Tan
The thunder god vine , Tripterygium hypoglaucum, is a toxic nectar plant distributed across China. A terpenoid, called triptolide (TRP), found in nectar can impair honeybees’ foraging responses, dance communication, and olfactory learning. In the present study, we tested the tolerances of the native honeybee Apis cerana and the introduced honeybee A. mellifera to short-term and long-term exposure to TRP. The results showed that introduced A. mellifera is more vulnerable in fatality to high concentrations of TRP sucrose solution (5 and 10 µg TRP mL −1 ) than A. cerana . We also compared the short-term and long-term exposure effects of TRP on olfactory learning and memory between the two honeybee species, and the olfactory learning and memory of both honey bee species showed impaired performance after both 2 h or 7 days of being fed with TRP sucrose solution. However, A. cerana showed a higher tolerance and resistance to TRP toxin than A. mellifera. Our results support a coevolution hypothesis in that the native species A. cerana has higher toxin tolerance than the introduced species A. mellifera .
研究领域:
昆虫学
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毒理学
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生态学
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DOI
PubMed
高影响因子
Nanomedicine
·
2025
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IF 3.9
Jingmei Zhou,Min Lin,Yan Mo,Ruiyue Dang,Jin Zhou,Chengmin Li,Xin Deng,Alaa Aldeen Alsaeedi,Yingqi Zhao,Juan Huang,Lijuan Ma,Xueping Feng,Yong Liu,Yunyun Wang
Aim To develop docetaxel (DTX) and triptolide (TPL) polymer micelles (DTX/TPL-PMs) with synergistic anti-cancer effect and to evaluate their anti-cancer activity.Methods DTX/TPL-PMs were prepared by thin-film hydration. The drug loading (DL%), encapsulation efficiency (EE%), and cumulative release rate (CR%) were determined using HPLC. The anti-cancer activity was assessed using CCK-8, inverted microscopy, and laser scanning confocal microscope (LSCM).Results DTX/TPL-PMs exhibited the average particle size of 178.58 ± 1.66 nm with a polydispersity index (PDI) of 0.102 ± 0.018 and a zeta potential of 1.19 ± 0.12 mV. These micelles showed a high EE% (89.43%) and a DL% (5.21%). In vitro release studies of DTX/TPL-PMs revealed that the loaded drug exhibited a slow-release phase in physiological fluids and a rapid-release phase under acidic conditions. Compared with the free DTX/TPL drugs, DTX/TPL-PMs were more readily taken up by cancer cells. The cytotoxicity of DTX/TPL-PMs was significantly higher than that of the free drugs, which showed stronger growth inhibitory effects and higher apoptosis rates in cancer cells.Conclusion The research results demonstrate that DTX/TPL-PMs enhance the therapeutic efficacy against malignancies, while reducing adverse effects. It holds potential as an effective nanotherapeutic for combination chemotherapy and represents a promising clinical strategy.
研究领域:
药剂学
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纳米医学
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肿瘤学
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药物递送系统
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PubMed
高影响因子
Journal of Biomedical Nanotechnology
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2022
·Vol. 18
·期 10
·2417-2432
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IF 3.641
Qin ZhongHua,Yu GuiPing,Li Ran,Zhao Jun
Triptolide (as an effective antitumor drug) is limited in clinical application because of its poor solubility and absorption in-vivo. Herein, we prepared folic acid modified polymer micelles to encapsulate triptolide and enhance its biologicalavailability coupled with antitumor
effect. We prepared nano-micelles of triptolide through thin lipid film hydrational method. Physical properties and in vitro release characterization of Fol-Plla-cl-Peg-Plla-cl-Tmicelles were evaluated, while bioavailability of the formulation in rats was investigated. Tumor targeting
potential of micelles was determined by observing the uptake of A549 cells. In-Vitro antitumor activity of micelles and free triptolide (API) was investigated with MTT assay. The prepared polymer material exhibited no cytotoxicity. The particle size distribution of Fol-Plla-cl-Peg-Plla-cl-T
micelles was uniform and small, with good stability and high efficiency of entrapment. Triptolide In-Vitro release from micelles demonstrated slow and continuous released for 24 h. Compared with API, the half-life of micelles was prolonged, whilst its bioavailability in-vivo
was increased by about 6.35 times. More importantly, Fol-Plla-cl-Peg-Plla-cl-T micelles significantly improved the antitumor activity of triptolide and showed good tumor targeting potential. Fol-Plla-cl-Peg-Plla-cl-T micelles could improve the bioavailability and antitumor activity of triptolide,
amid demonstration of good tumor targeting and high safety.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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DOI
高影响因子
Evidence-based Complementary and Alternative Medicine
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2021
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IF 2.63
Xubin Bao,Cai Chen,Liyong Yuan
Triptolide (T10) is a common anti-inflammatory and analgesic drug. However, the activation of microglia and elimination of the corresponding inflammatory response are new targets for the treatment of neuropathic pain. Chemokine CCL (CCL2) is a key mediator for activating microglia. In this study, the effects of triptolide on the activation and polarization of microglia cells and CCL2 and its corresponding receptor, chemokine receptor 2 (CCR2), were mainly discussed. Microglia were stimulated with 1 μg/mL lipopolysaccharide (LPS) and pretreated with 10, 20, and 40 nM T10 and CCR2 antagonist (RS102895), respectively. The quantitative polymerase chain reaction (QPCR) and western blot results showed that T10 could obviously inhibit the upregulation of CCL2 and CCR2 induced by LPS stimulation in microglia cells, inhibit the fluorescence intensity of glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS) antibody immunostaining in cells, and upregulate the fluorescence intensity of arginase 1 antibody in cells. The expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) was inhibited in a dose-dependent manner. RS102895 can significantly reverse the activation and M2 polarization of microglia pretreated with 40 nM T10 and weaken the anti-inflammatory effect of T10. The addition of CCL2 did not extremely affect the function of RS102895. T10 may inhibit microglia activation and M1 polarization by inhibiting the expression of CCL2 and CCR2, promoting M2 polarization, reducing the level of inflammatory factors in cells, and exerting its analgesic effect, which is worthy of clinical promotion as a drug for neuropathic pain.
研究领域:
药理学
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神经科学
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免疫学
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DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2025
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IF 3
Min Yan,Lan Zhang,Junwei Zhao,Yaning Ge,Kai Hu,Zijuan Zhang,Xin Zhu,Xiangxiang Wu,Zhenqiang Zhang,Huahui Zeng
Objective This study developed triptolide-loaded liposomes (TPL) for intranasal delivery to mitigate systemic toxicity of free triptolide (TP) while enhancing therapeutic efficacy in neuroinflammatory and Alzheimer’s disease (AD) models.Methods Biodistribution of luciferin liposomes was compared across oral, intravenous, and nasal routes using in vivo imaging. TPL was prepared via thin-film hydration with optimized phospholipid/cholesterol ratios. Safety profiles of intranasal TPL and TP were evaluated in wild-type mice. Efficacy was assessed in LPS-induced neuroinflammation and APP/PS1 AD models through behavioral tests, histopathology, and molecular analyses.Results Nasal administration demonstrated superior brain accumulation of luciferin liposomes compared to oral and intravenous routes. Optimized TPL exhibited spherical morphology with appropriate particle size, high drug encapsulation efficiency, and sustained release characteristics. Intranasal TPL showed reduced systemic toxicity relative to free TP. In disease models, TPL significantly improved behavioral and cognitive performance in both LPS-treated and APP/PS1 mice. Histopathological analysis revealed attenuated neuronal damage, reduced Aβ plaque deposition, and suppressed glial activation (IBA-1 and GFAP expression). Molecular studies demonstrated downregulation of pro-inflammatory cytokines (TNF-α, IL-1β, COX-2, IL-6) and apoptosis markers (Bax, Caspase-3), accompanied by increased expression of survival-related proteins (p-Akt, Bcl-2).Conclusions The nasal TPL delivery system effectively enhances brain targeting of TP while reducing systemic exposure. Its multimodal mechanisms—including anti-inflammatory effects, amyloid pathology modulation, and apoptosis regulation—support therapeutic potential for neurodegenerative disorders.
研究领域:
神经药理学
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药物递送系统
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神经退行性疾病
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纳米医学
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2026
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IF 5.6
Tao Ling,Liu Yidan,Chen Xintao,Zhou Wenjing,Zhang Ni,Zang Zhenzhong,Li Zhe,Zhang Hua,Liu lili,Chen Limei,Guan Yongmei,Zhu Weifeng
Rheumatoid arthritis (RA) is a prevalent chronic systemic autoimmune disease that induces irreversible joint erosion and disability. Triptolide (TP) exerts potent therapeutic efficacy against RA. However, conventional transdermal TP formulations provoke severe skin irritation upon long-term application, substantially restricting their clinical translation. To overcome these limitations, we fabricated water-stable cross-linked γ-cyclodextrin metal–organic frameworks (COFs) for TP encapsulation and synthesized phospholipid-modified polypyrrole nanoparticles (PPy-PC NPs) with outstanding photothermal performance. A composite hydrogel designated TP@COF-PPy NPs gel was constructed to integrate photothermal therapy (PTT) and transdermal delivery, enabling synergistic RA intervention with lowered systemic and cutaneous toxicity. The composite gel afforded a TP loading capacity of (454.81 ± 40.17) μg/g, accompanied by favorable structural stability, excellent photothermal properties and satisfactory rheological characteristics. In vitro release experiments revealed that the gel displayed a unique biphasic release profile and compensated for the inadequate late-stage drug leakage of pure TP gel. Notably, PTT irradiation neither damaged the gel structure nor induced abrupt drug burst release. In vitro transdermal assays verified that the optimized gel boosted cutaneous permeation, diminished skin drug retention, and facilitated deep-tissue drug penetration; auxiliary PTT further elevated permeation efficiency and mitigated skin toxic responses. Pharmacological evaluations confirmed that the composite gel halted RA progression via suppressing inflammatory cascades, modulating bone destruction and restoring immune homeostasis. The gel combined with PTT yielded markedly superior therapeutic outcomes relative to the gel monotherapy and clinical positive agents (methotrexate, diclofenac sodium). Biosafety assessments validated that the combinatorial regimen possessed superior skin biocompatibility, and no obvious hepatic, renal, or reproductive toxicities were detected in collagen-induced arthritis rats following 30-day continuous administration. Collectively, this study proves that PTT-augmented transdermal TP delivery represents a safe, promising strategy for efficient RA management.
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高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2019
·Vol. 33
·期 11
·e22394
·
IF 2.965
Ling-Yan Xu,Wei Wu,Rui Cheng,Li-Xin Sun,Zhen-Zhou Jiang,Lu-Yong Zhang,Zun-Jian Zhang,Yu-Wen Su,Xin Huang
Triptolide (TP), a major active ingredient of Tripterygium wilfordii , exerts potent immunosuppressive effects in the treatment of rheumatoid arthritis but is not widely used in clinical practice due to its multiorgan toxicity, particularly hepatotoxicity, nephrotoxicity, and reproductive toxicity. An LC-MS/MS approach was employed to explore the endocrine-disrupting effects of TP. The endocrine-disrupting effects of various concentrations (0-100 nM) of TP for 48 hour were firstly investigated using an in vitro model (H295R cell line). It was found that TP did not decrease cell viability. The transcriptional levels of steroidogenic enzymes in H295R cells were assessed by quantificational real-time polymerase chain reaction. The possible adrenal and endocrine effects of oral administration of TP (0, 50, and 500 μg/kg) for 28 days on both normal and collagen-induced arthritis (CIA) rats were also explored. The serum and adrenal tissue hormone levels (corticosterone and progesterone) and adrenal histopathology were analyzed, with the results that TP significantly decreased the level of cortisol in H295R cells and the level of plasma corticosterone in both normal and CIA rats. Histological alterations in adrenal cortex were observed at the dose of 500 μg/kg. Exposure to TP for 48 hour had an obvious inhibitory effect on the messenger RNA transcript levels of HSD3B2 , CYP21A2 , CYP17A1 , and CYP11B1 , which is essential for the synthesis of corticosteroids. In a word, TP leads to the disorder of corticosteroid synthesis and secretion, and corticosteroid may be a potential biomarker for the treatment of multiorgan toxicity of TP.
研究领域:
药理学
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毒理学
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内分泌学
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免疫学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2021
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IF 6.291
Ke Wang,Huina Hu,Wenbo Cui,Xuelian Zhang,Qi Tang,Nuan Liu,Xianyong Lan,Chuanying Pan
As a widely existing traditional Chinese medicine component, TP (triptolide) has serious reproductive toxicity which causes severe damage to the reproductive system and limits its application prospect. TP and MET (metformin) have shown great potential in combined with each other in anticancer and anti-inflammatory. Whether metformin can resist the reproductive toxicity caused by triptolide, the effects of MET on TP-induced reproductive capacity has not been reported. In this study, metformin was used to investigate the therapeutic effect on reproductive toxicity induced by TP in rat. The results showed that metformin had significant therapeutic effects on oxidative stress damage, destruction of the blood-testosterone barrier and apoptosis. And it proved that its therapeutic effect is mainly to restore the structural and functional stability of testis through antioxidant stress. It will provide guidance for the treatment of reproductive toxicity caused by TP and the adjuvant detoxification of TP application.
研究领域:
药理学
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生殖生物学
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毒理学
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PubMed
高影响因子
Nature Communications
·
2020
·Vol. 11
·期 1
·1-12
·
IF 12.121
Tu Lichan,Su Ping,Zhang Zhongren,Gao Linhui,Wang Jiadian,Hu Tianyuan,Zhou Jiawei,Zhang Yifeng,Zhao Yujun,Liu Yuan,Song Yadi,Tong Yuru,Lu Yun,Yang Jian,Xu Cao,Jia Meirong,Peters Reuben J.,Huang Luqi,Gao Wei
Triptolide is a trace natural product of Tripterygium wilfordii . It has antitumor activities, particularly against pancreatic cancer cells. Identification of genes and elucidation of the biosynthetic pathway leading to triptolide are the prerequisite for heterologous bioproduction. Here, we report a reference-grade genome of T. wilfordii with a contig N50 of 4.36 Mb. We show that copy numbers of triptolide biosynthetic pathway genes are impacted by a recent whole-genome triplication event. We further integrate genomic, transcriptomic, and metabolomic data to map a gene-to-metabolite network. This leads to the identification of a cytochrome P450 (CYP728B70) that can catalyze oxidation of a methyl to the acid moiety of dehydroabietic acid in triptolide biosynthesis. We think the genomic resource and the candidate genes reported here set the foundation to fully reveal triptolide biosynthetic pathway and consequently the heterologous bioproduction.
研究领域:
植物生物学
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基因组学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）